How does buprenorphine fair as an alternative to methadone for treating opioid dependence?


There are approximately 15-39 million opioid users in the world, (Degenhardt, 2012) and while opioid use is prevalent in a relatively small portion of the global population (0.6-0.8%); it poses significant health problems to both the individual and community. These risks include the spread of infectious disease such as HIV and hepatitis B & C, as well as overdose and death (Degenhardt, 2011; Mather, 2008; Nelson, 2011).

Currently, the main treatment for opioid dependence is methadone maintenance treatment (MMT). Although MMT can result in continued dependence if a dose is skipped due to its lengthy withdrawal process.

A recent Cochrane systematic review (Mattick et al, 2014) investigates the use of buprenorphine maintenance therapy as an alternative. Opposed to methadone and heroin, which are full agonists, buprenorphine is a partial agonist, thus exerting fewer effects on receptor sites. This results in an easier withdrawal phase, due to the longer duration of action and the option of alternate-day dosing.


A comprehensive search was conducted of the published literature, bibliographic databases, and trial registers. From an identified initial 6,495 studies, the reviewers included 31 studies (5,430 participants) in the final analysis.

  • 20 studies compared methadone and buprenorphine
  • 11 studies compared buprenorphine and placebo
  • 11 studies used flexible-dosing (Fischer, 1999) whereby dosing is titrated to participants’ preference within an upper and lower limit
  • 20 studies used fixed-dosing, which did not allow for adjustment of dosing after stabilisation

The primary outcomes of this review included treatment retention, opioid use (self-report and urine screen), other substance use (self-report and urine screen), criminal activity, and mortality. Secondary outcomes included adverse medication effects, and physical and psychological health (Mattick et al, 2014).

It's estimated that

It’s estimated that 15-39 million people worldwide are regular opioid users.


Buprenorphine maintenance versus placebo:

  • Buprenorphine (all doses 2mg to ≥16mg) was more effective than placebo at patient retention
  • Only high dose Buprenorphine (≥16mg) was more effective than placebo in supressing illicit opioid use (measured by urinalysis)

Buprenorphine maintenance versus methadone maintenance:

  • Buprenorphine in flexible doses was less effective than methadone in retaining participants, nor was a difference observed in the suppression of opioid use for the participants who remained in treatment (measured by urinalysis)
  • In low-dose studies, methadone (≤40mg) was more likely to retain participants than low-dose Buprenorphine (2-6mg)
  • There was no difference between medium-dose buprenorphine (7-15mg) and methadone (40-85mg) in retention or suppression of illicit opioid use
  • Additionally, there was no difference between high dose buprenorphine (≥16mg) and methadone (≥85mg) in retention or heroin use
Photograph: Danny Lawson/PA Archive/PA Photos

This review concluded that methadone is superior to buprenorphine in retaining people in treatment, and methadone equally suppresses illicit opioid use. Photograph: Danny Lawson/PA Archive/PA Photos


  • While this review shows that high-dose buprenorphine is an effective maintenance treatment for heroin compared to placebo, fixed flexible-dosing methadone proved more superior to buprenorphine at participant retention
  • Additionally, as flexible dosing is uncommon in clinical practice, the fixed dosing findings are more relevant to primary care (Mattick et al, 2014)
  • As both maintenance therapies are effective in the suppression of heroin use, buprenorphine should be supported in cases where methadone cannot be tolerated or administered
  • Additionally, buprenorphine could be provided as an alternative choice to the patient, when they may circumstantially benefit from the alternate-day dosing, not permitted in methadone maintenance (Mattick et al, 2014)

The Cochrane reviewers suggest that for people who cannot tolerate methadone, buprenorphine can be used as a maintenance treatment


Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD002207. DOI: 10.1002/14651858.CD002207

Degenhardt L, Hall W. Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet 2012;379(9810):55–70. [PubMed abstract]

Degenhardt L, Bucello C, Mathers B, Briegleb C, Ali H, Hickman M, et al. Mortality among regular or dependent users of heroin and other opioids: A systematic review and meta-analysis of cohort studies. Addiction 2011;106(1): 32–51. [PubMed abstract]

Mathers BM, Degenhardt L, Phillips B, Wiessing L, Hickman M, Strathdee SA, et al. Global epidemiology of  injecting drug use and HIV among people who inject drugs: a systematic review. Lancet 2008;372(9651):1733–45. [PubMed abstract]

Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 2011;378(9791):571–83. [PubMed abstract]

Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger G, et al. Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Addiction 1999;94(9):1337–47. [PubMed abstract]

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